{"title":"The effects of sex hormone therapy on kidney function","authors":"Ellen F. Carney","doi":"10.1038/s41581-025-00966-x","DOIUrl":"https://doi.org/10.1038/s41581-025-00966-x","url":null,"abstract":"<p>Progression of chronic kidney disease (CKD) is generally faster in cisgender men than cisgender women, suggesting a protective effect of female sex. An observational study in 44 transgender individuals who initiated either feminizing (estradiol and antiandrogens) or masculinizing (testosterone) hormone therapy provides new insights into the effects of sex hormones on the kidney. “This population provides a unique opportunity to study the effects of well-defined changes in sex hormone concentrations,” says researcher Sarah van Eeghen.</p><p>Sex hormone therapy also resulted in changes in the concentrations of tubular injury biomarkers, with decreases in urinary NGAL, MCP1 and YKL-40 with feminizing therapy and increases in urinary YKL-40 and plasma TNFR1 with masculinizing therapy. “These results suggest that estradiol may protect against early tubular injury and inflammation, whereas testosterone may promote kidney inflammation,” comments van Eeghen. In addition, a plasma proteomics analysis identified several circulating proteins with kidney-protective properties that increased during feminizing therapy and/or decreased during masculinizing therapy. Many of these proteins were positively associated with estradiol and negatively associated with testosterone, including proteins with roles in endothelial function, modulation of inflammation and preservation of kidney structural integrity.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"46 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Surabhi R. Madhvapathy, Soongwon Cho, Elisa Gessaroli, Eleonora Forte, Yirui Xiong, Lorenzo Gallon, John A. Rogers
{"title":"Implantable bioelectronics and wearable sensors for kidney health and disease","authors":"Surabhi R. Madhvapathy, Soongwon Cho, Elisa Gessaroli, Eleonora Forte, Yirui Xiong, Lorenzo Gallon, John A. Rogers","doi":"10.1038/s41581-025-00961-2","DOIUrl":"https://doi.org/10.1038/s41581-025-00961-2","url":null,"abstract":"<p>Established clinical practices for monitoring kidney health and disease — including biopsy and serum biomarker analysis — suffer from practical limitations in monitoring frequency and lack adequate sensitivity for early disease detection. Engineering advances in biosensors have led to the development of wearable and implantable systems for monitoring of kidney health. Non-invasive microfluidic systems have demonstrated utility in the detection of kidney-relevant biomarkers, such as creatinine, urea and electrolytes in peripheral body fluids such as sweat, interstitial fluid, tears and saliva. Implantable systems may aid the identification of early transplant rejection through analysis of organ temperature and perfusion, and enable real-time assessment of inflammation through the use of thermal sensors. These technologies enable continuous, real-time monitoring of kidney health, offering complementary information to standard clinical procedures to alert physicians of changes in kidney health for early intervention. In this Review, we explore devices for monitoring renal biomarkers in peripheral biofluids and discuss developments in implantable sensors for the direct measurement of the local, biophysical properties of kidney tissue. We also describe potential clinical applications, including monitoring of chronic kidney disease, acute kidney injury and allograft health.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"46 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giovambattista Capasso, Casper F. M. Franssen, Alessandra F. Perna, Ziad A. Massy, Robert I. Menzies, Carmine Zoccali, Alessandro Tessitore, Maiken Nedergaard, Mark D. Okusa, Alberto Ortiz, Carsten A. Wagner, Robert J. Unwin
{"title":"Drivers and mechanisms of cognitive decline in chronic kidney disease","authors":"Giovambattista Capasso, Casper F. M. Franssen, Alessandra F. Perna, Ziad A. Massy, Robert I. Menzies, Carmine Zoccali, Alessandro Tessitore, Maiken Nedergaard, Mark D. Okusa, Alberto Ortiz, Carsten A. Wagner, Robert J. Unwin","doi":"10.1038/s41581-025-00963-0","DOIUrl":"https://doi.org/10.1038/s41581-025-00963-0","url":null,"abstract":"<p>Cognitive impairment is highly prevalent among individuals with chronic kidney disease (CKD). Despite its high prevalence, the contributing factors and mechanisms underlying brain–kidney dysfunction in CKD remain poorly understood. However, advances in neuroscience, including novel imaging techniques and cognitive assessment methods, have begun to clarify this complex relationship. Several factors contribute directly to cognitive decline in people with CKD, including accumulation of uraemic toxins, microvascular damage, malnutrition, chronic inflammation and disruptions in key neuroprotective pathways, such as those involving Klotho and the glymphatic system. These factors are also linked to the accelerated ageing observed in people with CKD, a key contributor to cognitive decline. However, most studies on cognition in people with CKD have been cross-sectional and associative, offering limited insight into causation. Research advances, such as studies on the effect of uraemic toxins on the blood–brain barrier and the role of the endothelial glycocalyx in vascular damage, offer promising new directions. Emerging data from longitudinal cohort studies are also enhancing our understanding of these processes, with potential implications for both the treatment of CKD-related cognitive decline and the broader issue of cognitive dysfunction in ageing populations. Here, we examine key mechanisms linking CKD to cognitive decline and consider potential therapeutic interventions.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"45 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dialysis and cognitive impairment","authors":"Chris W. McIntyre, Arsh Jain","doi":"10.1038/s41581-025-00960-3","DOIUrl":"https://doi.org/10.1038/s41581-025-00960-3","url":null,"abstract":"<p>People with chronic kidney disease who require maintenance dialysis characteristically experience accelerated and aggravated cognitive decline compared with those with advanced kidney disease who are not receiving this form of kidney replacement therapy. This effect is inadequately appreciated, but of crucial importance to patients, their carers and the health-care systems that support them. Although many of the comorbid conditions prevalent in this patient population have the potential to affect brain structure and function, an evolving body of evidence indicates that the dialysis therapy itself has a central role in the pathophysiology of progressive cognitive impairment. Both haemodialysis and peritoneal dialysis are associated with structural and functional changes in the brain that can lead to characteristic short-term symptoms, such as headache, confusion, delirium and brain fog, as well as long-term reductions in cognitive functional ability. Here, we explore the mechanisms, both established and putative, underlying these effects and consider approaches to addressing this issue with both single and complex therapeutic interventions.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"31 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thoralf Niendorf, Thomas Gladytz, Kathleen Cantow, Jason M. Millward, Sonia Waiczies, Erdmann Seeliger
{"title":"Magnetic resonance imaging of renal oxygenation","authors":"Thoralf Niendorf, Thomas Gladytz, Kathleen Cantow, Jason M. Millward, Sonia Waiczies, Erdmann Seeliger","doi":"10.1038/s41581-025-00956-z","DOIUrl":"https://doi.org/10.1038/s41581-025-00956-z","url":null,"abstract":"<p>Renal hypoxia has a key role in the pathophysiology of many kidney diseases. MRI provides surrogate markers of oxygenation, offering a critical opportunity to detect renal hypoxia. However, studies that have assessed the diagnostic performance of oxygenation MRI for kidney disorders have provided inconsistent results because MRI metrics do not fully capture the complexity of renal oxygenation. Most oxygenation MRI studies are descriptive in nature and fail to detail the pathophysiological importance of the imaging findings. These limitations have restricted the clinical application of oxygenation MRI and the full potential of this technology to facilitate early diagnosis, risk prediction and treatment monitoring of kidney disease has not yet been realized. Understanding of the relationship between renal tissue oxygenation and MRI metrics, which is affected by kidney size, tubular volume fraction and renal blood volume fraction, and measurement of these factors using novel MR methods is imperative for correct physiological interpretation of renal MR oximetry findings. Next steps to enable the clinical adoption of MR oximetry should involve multidisciplinary collaboration to address standardization of acquisition and data analysis protocols and establish reference values of MRI metrics.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"6 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao-ming Meng, Li Wang, David J. Nikolic-Paterson, Hui-Yao Lan
{"title":"Innate immune cells in acute and chronic kidney disease","authors":"Xiao-ming Meng, Li Wang, David J. Nikolic-Paterson, Hui-Yao Lan","doi":"10.1038/s41581-025-00958-x","DOIUrl":"https://doi.org/10.1038/s41581-025-00958-x","url":null,"abstract":"<p>Acute kidney injury (AKI) and chronic kidney disease (CKD) are inter-related clinical and pathophysiological disorders. Cells of the innate immune system, such as granulocytes and macrophages, can induce AKI through the secretion of pro-inflammatory mediators such as cytokines, chemokines and enzymes, and the release of extracellular traps. In addition, macrophages and dendritic cells can drive the progression of CKD through a wide range of pro-inflammatory and pro-fibrotic mechanisms, and by regulation of the adaptive immune response. However, innate immune cells can also promote kidney repair after acute injury. These actions highlight the multifaceted nature of the way by which innate immune cells respond to signals within the kidney microenvironment, including interaction with the complement and coagulation cascades, cells of the adaptive immune system, intrinsic renal cells and infiltrating mesenchymal cells. The factors and mechanisms that underpin the ability of innate immune cells to contribute to renal injury or repair and to drive the progression of CKD are of great interest for understanding disease processes and for developing new therapeutic approaches to limit AKI and the AKI-to-CKD transition.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"15 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"GalNAc-T14-associated defects in B cell homing in IgA nephropathy","authors":"Susan J. Allison","doi":"10.1038/s41581-025-00964-z","DOIUrl":"https://doi.org/10.1038/s41581-025-00964-z","url":null,"abstract":"<p>IgA nephropathy (IgAN) is a common form of glomerulonephritis. Its pathogenesis has been linked to aberrant O-glycosylation of the IgA1 hinge region, which is thought to underlie the formation of IgA1-containing immune complexes that deposit in glomeruli. New insights suggest that IgA O-glycosylation may also affect additional processes, including mucosal immunity and B cell homing to mucosal and non-mucosal lymphoid tissues.</p><p>Sindhuri Prakash and colleagues initiated their study by identifying independent loss-of-function variants in an <i>N</i>-acetylgalactosaminyltransferase 14 (GalNAc-T14)-encoding gene, <i>GALNT14</i>, in a family segregating with IgAN (two people with biopsy-proven IgAN, one with IgA vasculitis and others with haematuria) and one individual with sporadic IgAN. Acetylgalactosaminyltransferases are enzymes that initiate the first step in the O-glycosylation of IgAN, suggesting a pathogenic role for the identified variants.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"6 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Devon A. Barnes, Luiz Ladeira, Rosalinde Masereeuw
{"title":"From big data to smart decisions: artificial intelligence in kidney risk assessment","authors":"Devon A. Barnes, Luiz Ladeira, Rosalinde Masereeuw","doi":"10.1038/s41581-025-00962-1","DOIUrl":"https://doi.org/10.1038/s41581-025-00962-1","url":null,"abstract":"Artificial intelligence approaches that link patient data with chemical-induced kidney injury patterns are revolutionizing nephrotoxicity risk assessment. Substantial progress has been made in the development of integrated approaches that leverage big data, molecular profiles and toxicological understanding to identify at-risk patients, provide insights into molecular mechanisms and advance predictive nephrology.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"28 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing the effect of social and environmental burdens on kidney disease","authors":"Mukoso N. Ozieh, Bessie A. Young","doi":"10.1038/s41581-025-00955-0","DOIUrl":"https://doi.org/10.1038/s41581-025-00955-0","url":null,"abstract":"Social and environmental exposures are strong drivers of health inequity and adverse health outcomes. However, data from studies that examine the longitudinal effect of social and environmental exposure burdens on kidney disease outcomes are limited. The environmental justice index–social environmental ranking, although imperfect, provides an important tool to address this gap in knowledge.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"140 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nermin Ahmed, Carolina Dalmasso, Meghan B. Turner, Gertrude Arthur, Cole Cincinelli, Analia S. Loria
{"title":"From fat to filter: the effect of adipose tissue-derived signals on kidney function","authors":"Nermin Ahmed, Carolina Dalmasso, Meghan B. Turner, Gertrude Arthur, Cole Cincinelli, Analia S. Loria","doi":"10.1038/s41581-025-00950-5","DOIUrl":"https://doi.org/10.1038/s41581-025-00950-5","url":null,"abstract":"<p>Obesity is associated with severe consequences for the renal system, including chronic kidney disease, kidney failure and increased mortality. Obesity has both direct and indirect effects on kidney health through several mechanisms, including activation of the renin–angiotensin system, mechanical compression, inflammation, fibrosis, increased filtration barrier permeability and renal nerve activity. The expansion of adipose tissue through hypertrophy and hyperplasia can induce haemodynamic changes that promote glomerular hyperfiltration to compensate for the greater metabolic demands of the increased body weight. Adipose expansion is also associated with the release of adipokines and pro-inflammatory cytokines, hyperinsulinaemia and insulin resistance, which exert direct and indirect effects on kidney function via various mechanisms. Increased uptake of fatty acids by the kidney leads to alterations in lipid metabolism and lipotoxicity, also contributing to the pro-inflammatory and pro-fibrotic environment. The role of the adipose tissue–brain–kidney axis in the obesity-associated decline in renal function is sustained by studies showing that stimulation of adipose tissue sensory neurons by locally released factors increases renal sympathetic nerve activity. Conversely, pre-existent kidney disease can contribute to adipose dysfunction through the accumulation of uraemic toxins and hormonal changes. These findings highlight the importance of crosstalk between adipose tissue and the kidneys and provide insights into the mechanisms underlying the associations between obesity and kidney disease.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"89 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}